PMID- 31828395
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20200713
IS  - 1432-2072 (Electronic)
IS  - 0033-3158 (Linking)
VI  - 237
IP  - 3
DP  - 2020 Mar
TI  - Spermidine, a positive modulator of the NMDA receptor, facilitates extinction and 
      prevents the reinstatement of morphine-induced conditioned place preference in 
      mice.
PG  - 681-693
LID - 10.1007/s00213-019-05403-z [doi]
AB  - RATIONALE: Individuals with opioid use disorders often relapse into drug-seeking 
      behavior after recalling memories linked to the drug use experience. Improving 
      extinction efficacy has been used as a strategy to treat substance use disorders 
      and suppress relapse. Although N-methyl-D-aspartate receptor (NMDAr) agonists 
      facilitate acquisition, consolidation, and extinction, no study has addressed 
      whether spermidine (SPD), a natural polyamine ligand of the NMDA receptor, 
      facilitates the extinction and reinstatement of morphine-induced conditioned 
      place preference (CPP). OBJECTIVES AND METHODS: The aim of the present study was 
      to investigate the effect of SPD, an NMDAr agonist, on the extinction and 
      reinstatement of morphine-induced CPP in mice. Adult male albino Swiss mice 
      received saline (0.9% NaCl) or morphine (5 mg/kg) intraperitoneally (i.p.) and 
      were respectively confined to a black or a white compartment for 30 min for four 
      consecutive days for CPP induction. SPD (10-30 mg/kg, i.p.) or ifenprodil (NMDAr 
      antagonist, 0.1-1 mg/kg, i.p.) were injected 15 min before extinction training. 
      RESULTS: SPD and ifenprodil facilitated the extinction of morphine-induced CPP. 
      SPD treatment during the extinction period impaired reinstatement induced by a 
      priming dose of morphine (1.25 mg/kg). Ifenprodil (0.1 mg/kg) prevented the 
      facilitatory effect of spermidine on the extinction of morphine-induced CPP but 
      did not prevent reinstatement induced by morphine. CONCLUSIONS: These results 
      suggest that SPD facilitated the extinction of morphine-induced CPP by modulating 
      the polyamine binding site of the NMDA receptor. Our findings reveal important 
      effects of SPD and ifenprodil on the re-exposure-induced decrease in 
      morphine-induced CPP, which may be promising for developing novel pharmacological 
      strategies to treat opioid use disorder.
FAU - Girardi, Bruna A
AU  - Girardi BA
AD  - Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of 
      Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, 
      97105-900, Brazil.
FAU - Fabbrin, Shaiana
AU  - Fabbrin S
AD  - Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of 
      Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, 
      97105-900, Brazil.
FAU - Wendel, Arithane L
AU  - Wendel AL
AD  - School of Pharmacy, Center of Health Sciences, Federal University of Santa Maria, 
      Santa Maria, RS, 97105-900, Brazil.
FAU - Mello, Carlos F
AU  - Mello CF
AD  - Graduate Program in Pharmacology, Center of Health Sciences, Federal University 
      of Santa Maria, Santa Maria, RS, 97105-900, Brazil. cf.mello@smail.ufsm.br.
FAU - Rubin, Maribel A
AU  - Rubin MA
AUID- ORCID: 0000-0002-2763-9619
AD  - Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of 
      Exact and Natural Sciences, Federal University of Santa Maria, Santa Maria, RS, 
      97105-900, Brazil. marubin@smail.ufsm.br.
AD  - Graduate Program in Pharmacology, Center of Health Sciences, Federal University 
      of Santa Maria, Santa Maria, RS, 97105-900, Brazil. marubin@smail.ufsm.br.
LA  - eng
GR  - 306468/2014-0/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - 23038.004173/2019-93/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - 88882.182141/2018-01/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
PT  - Journal Article
DEP - 20191211
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 76I7G6D29C (Morphine)
RN  - U87FK77H25 (Spermidine)
SB  - IM
MH  - Animals
MH  - Conditioning, Classical/*drug effects/physiology
MH  - Drug-Seeking Behavior/*drug effects/physiology
MH  - Extinction, Psychological/*drug effects/physiology
MH  - Male
MH  - Mice
MH  - Morphine/*adverse effects/pharmacology
MH  - Motor Activity/drug effects/physiology
MH  - N-Methylaspartate/pharmacology
MH  - Opioid-Related Disorders/drug therapy/psychology
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/metabolism
MH  - Spermidine/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - Conditioned place preference
OT  - Morphine
OT  - NMDA receptor
OT  - Opioid use disorders
OT  - Reinstatement
OT  - Spermidine
EDAT- 2019/12/13 06:00
MHDA- 2020/07/14 06:00
CRDT- 2019/12/13 06:00
PHST- 2018/12/26 00:00 [received]
PHST- 2019/11/15 00:00 [accepted]
PHST- 2019/12/13 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2019/12/13 06:00 [entrez]
AID - 10.1007/s00213-019-05403-z [pii]
AID - 10.1007/s00213-019-05403-z [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2020 Mar;237(3):681-693. doi: 
      10.1007/s00213-019-05403-z. Epub 2019 Dec 11.